A remote household-based approach to influenza self-testing and antiviral treatment.

BACKGROUND: Households represent important settings for transmission of influenza and other respiratory viruses. Current influenza diagnosis and treatment relies upon patient visits to healthcare facilities, which may lead to under-diagnosis and treatment delays. This study aimed to assess the feasibility of an at-home approach to influenza diagnosis and treatment via home testing, telehealth care, and rapid antiviral home delivery. METHODS: We conducted a pilot interventional study of remote influenza diagnosis and treatment in Seattle-area households with children during the 2019-2020 influenza season using pre-positioned nasal swabs and home influenza tests. Home monitoring for respiratory symptoms occurred weekly; if symptoms were reported within 48 hours of onset, participants collected mid-nasal swabs and used a rapid home-based influenza immunoassay. An additional home-collected swab was returned to a laboratory for confirmatory influenza RT-PCR testing. Baloxavir antiviral treatment was prescribed and delivered to symptomatic and age-eligible participants, following a telehealth encounter. RESULTS: 124 households comprising 481 individuals self-monitored for respiratory symptoms, with 58 home tests administered. 12 home tests were positive for influenza, of which eight were true positives confirmed by RT-PCR. The sensitivity and specificity of the home influenza test were 72.7% and 96.2%, respectively. There were eight home deliveries of baloxavir, with 7 (87.5%) occurring within 3 hours of prescription and all within 48 hours of symptom onset. CONCLUSIONS: We demonstrate the feasibility of self-testing combined with rapid home delivery of influenza antiviral treatment. This approach may be an important control strategy for influenza epidemics and pandemics.

A randomized, multicenter study to determine the safety and efficacy of the immunoconjugate SGN-15 plus docetaxel for the treatment of non-small cell lung carcinoma.

PURPOSE: Chemotherapy prolongs survival and improves quality of life (QOL) for good performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Targeted therapies may improve chemotherapy effectiveness without worsening toxicity. SGN-15 is an antibody-drug conjugate (ADC), consisting of a chimeric murine monoclonal antibody recognizing the Lewis Y (Le(y)) antigen, conjugated to doxorubicin. Le(y) is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Le(y)-positive tumors in early phase clinical trials and was synergistic with docetaxel in preclinical experiments. This Phase II, open-label study was conducted to confirm the activity of SGN-15 plus docetaxel in previously treated NSCLC patients. EXPERIMENTAL DESIGN: Sixty-two patients with recurrent or metastatic NSCLC expressing Le(y), one or two prior chemotherapy regimens, and PS< or =2 were randomized 2:1 to receive SGN-15 200 mg/m2/week with docetaxel 35 mg/m2/week (Arm A) or docetaxel 35 mg/m2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350 mg/m2 was permitted in the second half of the study. Endpoints were survival, safety, efficacy, and quality of life. RESULTS: Forty patients on Arm A and 19 on Arm B received at least one treatment. Patients on Arms A and B had median survivals of 31.4 and 25.3 weeks, 12-month survivals of 29% and 24%, and 18-month survivals of 18% and 8%, respectively. Toxicity was mild in both arms. QOL analyses favored Arm A. CONCLUSIONS: SGN-15 plus docetaxel is a well-tolerated and active second and third line treatment for NSCLC patients. Ongoing studies are exploring alternate schedules to maximize synergy between these agents.

A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer.

INTRODUCTION: Denileukin diftitox, a chimeric protein, uses the cytocidal properties of diphtheria toxin to cells expressing interleukin-2 receptors. The aim of this study was to evaluate the efficacy and safety of denileukin diftitox in the treatment of advanced relapsed nonsmall cell lung cancer (NSCLC). PATIENTS AND METHODS: Multicenter phase II trial in patients with NSCLC with Eastern Cooperative Oncology Group PS 0-2, stage IIIB/IV at diagnosis, who had failed at least 1 previous chemotherapy regimen. Denileukin diftitox was infused at 18 microg/kg/d x 5 days, every 21 days for 6 cycles. RESULTS: For the 41 patients enrolled, the median age was 56 years (range, 21-80), 25 were men, and the median number of previous chemotherapy regimens was 2 (range, 1-5). The median number of treatment cycles was 2 (range, 1-6). By RECIST criteria, 18 (44%) had stable disease, 10 (24%) progressive disease, and 13 (32%) were not evaluable for response as they received less than 2 treatment cycles. The median time to disease progression was 1.8 months [range, 0.3-11.3; 95% confidence interval (CI) 1.3-2.6]. Median survival was 5.8 months (range, 0.3-33.6; 95% CI 3.4-11.4). The median follow-up time was 16.1 month. One death from myocarditis verified at autopsy was attributed to treatment. One grade 4 toxicity (vascular leak syndrome) was encountered, and 18 grade 3 toxicities, primarily gastro-intestinal, vascular leak syndrome, and constitutional symptoms. CONCLUSION: Denileukin diftitox at current dose schedule has limited activity in patients with previously treated NSCLC, manifested by disease control without impact on survival.

Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer.

PURPOSE: Generation of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay. RESULTS: No significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides (P < .001). CONCLUSION: IDM-2101 was well tolerated, and evidence of efficacy was suggested.

Thalidomide-induced organizing pneumonia.

Twenty medications are associated with drug-induced organizing pneumonia; however, thalidomide is not listed as a potential causative agent. Thalidomide (Thalomid, Celgene Corp., Summit, NJ), an angiogenesis inhibitor and immunomodulator that reduces tumor necrosis factor-alpha, is used for the treatment of multiple myeloma. We report a case of organizing pneumonia in a 58-year-old male with multiple myeloma treated with dexamethasone and thalidomide.